There are many prescription and non-prescription medications available for use in the treatment of symptoms caused by medical conditions such as colds and/or allergies (e.g. symptoms such as runny nose, fever, cough, and inflammation). In treating these symptoms it is often desirable to combine multiple pharmaceutical ingredients in a single pharmaceutically acceptable composition wherein each active ingredient is directed towards a specific symptom. However, each of the pharmaceutical ingredients generally have different physico-chemical properties and stability profiles.
Patients having difficulty swallowing therapeutic compositions in tablet and/or capsule form usually prefer ingesting therapeutic compositions in liquid “syrup” dosage form. The therapeutic composition(s) is dissolved or suspended in a carrier liquid and is delivered to the patient in a measured form (e.g. in a prepackaged gel package, disposable container, or in a bottle from which the patient or care giver can measure the appropriate dosage). Syrups also are often preferred dosage forms for formulation of pharmaceutical ingredients used for the treatment of cold, cough, congestion, and fever. Furthermore, syrups which produce a warming sensation provide a sense of immediate relief to symptoms are most preferred.
Liquid therapeutic compositions have been found to degrade over time. This degradation has been found to lead to inappropriate dosing of the therapeutic agent to patients and shortened shelf life of liquid therapeutic compositions. For example, phenylephrine hydrochloride (PHL) is a decongestant frequently used in over-the-counter (OTC) cough and cold preparations. PHL is a reactive molecule that undergoes reactions with numerous carrier solvent liquids (e.g. ethanol inter alia) commonly used in OTC preparations to form other species, with a corresponding decrease in the amount of active PHL in the product. This can lead to need to set shorter expiration times than may be considered optimum for OTC products. Therefore in designing a liquid carrier composition for OTC preparations care must be taken to prevent degradation and to stabilize actives like PHL.
The formulation of clear syrups containing less soluble drugs like Acetaminophen and Guaifenesin inter alia is challenging in terms of selection of suitable solvents systems. Some of these actives are soluble in different solvents in variable amount. So it is general practice to use combination of solvents like alcohol, propylene glycol, and glycerin inter alia in combination in syrup preparation. Alcohol is a preferred solvent along with other solvents in the syrup preparations.
Furthermore, less soluble actives tend to crystallize in liquid products when it stored at lower temperatures (e.g. 5° C.) during transportation and on the shelf at the pharmacy and the home. The factors influencing the crystallization include lower temperature, lack of appropriate solvents, shaking and presence of small crystals.
While many liquid carriers have been found to be suitable for liquid preparations, many liquid carriers (e.g. ethanol) are not suitable for use in OTC liquid preparations that are intended for children. In addition, the upper limit for a OTC liquid preparations intended for adult use is 10 wt %. Therefore, there is a strong need in the OTC therapeutic liquid composition industry to provide therapeutic liquid compositions and liquid carrier systems that solve the above identified problems.
There is a need for liquid therapeutic compositions containing hard-to-dissolve actives that overcomes the problems in the art.